Effects of impaired Ca²⁺ homeostasis on contraction in postinfarction myocytes

The significance of altered Ca²⁺ influx and efflux pathways on contractile abnormalities of myocytes isolated from rat hearts 3 wk after myocardial infarction (MI) was investigated by varying extracellular Ca²⁺ concentration ([Ca²⁺]₀, 0.6-5.0 mM) and pacing frequency (0.1-5.0 Hz). Myocytes isolated from 3-wk MI hearts were significantly longer than those from sham-treated (Sham) hearts (125 ± 1 vs. 114 ± 1 pro, P < 0.0001). At high [Ca²⁺]₀ and low pacing frequency, conditions that preferentially favored Ca²⁺ influx over efflux, Sham myocytes shortened to a greater extent than 3-wk MI myocytes. Conversely, under conditions that favored Ca²⁺ efflux (low [Ca²⁺]₀ and high pacing frequency), MI myocytes shortened more than Sham myocytes. At intermediate [Ca²⁺]₀ and pacing frequencies, differences in steady-state contraction amplitudes between Sham and MI myocytes were no longer significant. Collectively, the interpretation of these data was that Ca²⁺ influx and efflux pathways were subnormal in MI myocytes and that they contributed to abnormal cellular contractile behavior. Because Na⁺/Ca²⁺ exchange activity, but not whole cell Ca²⁺ current, was depressed in 3-wk MI rat myocytes, our results on steady-state contraction are consistent with, but not proof of, the hypothesis that depressed Na⁺/Ca²⁺ exchange accounted for abnormal contractility in MI myocytes. The effects of depressed Na⁺/Ca²⁺ exchange on MI myocyte mechanical activity were further evaluated in relaxation from caffeine-induced contractures. Because Ca²⁺ uptake by sarcoplasmic reticulum was inhibited by caffeine and with the assumption that intracellular Na⁺ and membrane potential were similar between Sham and MI myocytes, myocyte relaxation from caffeine- induced contracture can be taken as an estimate of Ca²⁺ extrusion by Na⁺/Ca²⁺ exchange. In MI myocytes, in which Na⁺/Ca²⁺ exchange activity was depressed, the half time of relaxation (1.54 ± 0.14 s) was significantly (P < 0.02) prolonged compared with that measured in Sham myocytes (1.10 ± 0.10 s).